Macular Degeneration: Tufail A

Cook HL, Patel PJ, Tufail A. · Moorfields Eye Hospital, City Road, London EC1V 2PD, UK. · Br Med Bull. · Pubmed #18334518 No free full text.

Abstract: BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blind registration in Western Europe and the third leading cause of blindness worldwide. METHODS: The management of AMD is discussed with a review of current and new treatments. RESULTS: Although there is no treatment for advanced dry AMD (geographic atrophy), there have been considerable advances in the management of neovascular AMD (nAMD). Established therapies for nAMD include laser photocoagulation and photodynamic therapy (PDT), but these have largely been superseded by agents which block the action of vascular endothelial growth factor (anti-VEGF agents). Current preventative strategies involve cessation of smoking and use of specific nutritional supplements to reduce the risk of developing nAMD. CONCLUSIONS: There have been exciting advances in the treatment of nAMD and increased understanding of the genetics and pathogenic mechanisms involved will hopefully lead to the development of new therapies in the future.

Chen FK, Uppal GS, MacLaren RE, Coffey PJ, Rubin GS, Tufail A, Aylward GW, Da Cruz L. · Moorfields Eye Hospital, London, UK. · Clin Experiment Ophthalmol. · Pubmed #19459869 No free full text.

Abstract: BACKGROUND: To describe the 2- to 4-year visual and microperimetry outcomes of autologous retinal pigment epithelium (RPE)-choroid graft in patients with neovascular age-related macular degeneration (AMD). METHODS: In this retrospective cohort study, 12 patients with subfoveal neovascular AMD who had undergone autologous RPE-choroid graft between August 2004 and June 2005 were reviewed. Change in visual acuity (VA), contrast sensitivity (CS), fixation stability and retinal sensitivity on microperimetry after 2-3 years and the rates of late postoperative complications were examined. RESULTS: Patients were followed for 26-48 months (mean, 39). Median preoperative VA (logMAR) was 0.87 but declined to 1.43 (1 year), 1.46 (2 years) and 1.38 (3 years), P = 0.001. Median CS (logCS) was 0.75 preoperatively but declined to 0.45 at 2 years. Six patients had serial microperimetry. Fixation stability declined in 1 but improved in 2 patients. All 6 had decline in retinal sensitivity over the graft during follow up. Retinal detachment did not occur after 12 months but 8 developed epiretinal membrane, 12 had cystic retinal change over the graft and 4 developed recurrent choroidal neovascularization. However, 10 grafts retained autofluorescence signal at 18-48 months of follow up. CONCLUSIONS: Autologous RPE-choroid graft can maintain VA, stable fixation and retinal sensitivity in some patients for over 3 years. The spatial correlation between graft autofluorescence, outer retinal structures on optical coherence tomography and retinal sensitivity are consistent with photoreceptor cell rescue. However, we caution the use of this technique as there is high complication rate and delayed loss of retinal function.

Patel PJ, Chen FK, Rubin GS, Tufail A. · Moorfields Eye Hospital, London, United Kingdom. · Invest Ophthalmol Vis Sci. · Pubmed #19218618 No free full text.

Abstract: PURPOSE: To describe the intersession repeatability of contrast sensitivity (CS) measurement using Pelli-Robson charts in patients with age-related macular degeneration. METHODS: Repeatability was calculated from three measurements of CS over a 12-week period using a standardized protocol in 107 nontreated eyes of 107 patients with age-related macular degeneration who were enrolled in an ongoing clinical trial. RESULTS: Data from 91 patients were included in the analysis, with a 95% coefficient of repeatability of 7 letters (0.35 log CS), ranging from 6 letters for 32 eyes with drusen only to 8 letters for patients with late AMD (macular scars or geographic atrophy). Three (3%) of these stable patients had an apparent six or more letter reduction in contrast sensitivity at the week 1 visit compared with baseline. CONCLUSIONS: There is a high intersession test-retest variability of Pelli-Robson CS scores in patients with AMD, with implications for AMD clinical trial design. Although a change criterion of six or more letters may be an adequate end point in clinical trials for patients with early AMD, a larger change criterion may be necessary for clinical trials of patients with late AMD.

Patel PJ, Chen FK, da Cruz L, Tufail A. · Moorfields Eye Hospital, London, United Kingdom. · Invest Ophthalmol Vis Sci. · Pubmed #18676631 No free full text.

Abstract: PURPOSE: To describe the rate of automated segmentation error in Stratus optical coherence tomography (OCT) scans in consecutive patients with neovascular age-related macular degeneration (nAMD) receiving treatment and to investigate the effect of the segmentation error on automated retinal thickness measures and whether further imaging reduces the rate of segmentation error. METHODS: A retrospective analysis of fast macular thickness map (FMTM) protocol OCT scans of 50 eyes of 50 consecutive patients with nAMD. Each line scan was analyzed for segmentation error with manual measurement of the center-point retinal thickness allowing calculation of the percentage error in automated thickness. OCT scanning was repeated to overcome segmentation error. RESULTS: Segmentation error was detected in 45 (90%) of the 50 patients with 37 (74%) patients having an error affecting the central 1-mm subfield. Scan sets with a high central segmentation error score (two or more line scans affected of six) had a significantly greater error in automated center-point retinal thickness than scan sets with a low error score (20% compared with 3%, P < 0.000005). Central subfield segmentation error persisted in 30 (60%) patients despite repeat scanning. CONCLUSIONS: There is a high rate of segmentation error in OCT scans of patients with nAMD who are undergoing treatment, leading to errors in automated central retinal thickness measurement. The authors recommend manual measurement of central macular thickness when two or more line scans are affected by segmentation error in the central 1-mm subfield. Repeated scanning reduced the rate of error but did not eliminate the problem.

Patel PJ, Chen FK, Rubin GS, Tufail A. · Moorfields Eye Hospital, London, United Kingdom. · Invest Ophthalmol Vis Sci. · Pubmed #18566455 No free full text.

Abstract: PURPOSE: To describe the intersession repeatability of visual acuity measures obtained with Early Treatment of Diabetic Retinopathy Study (ETDRS) charts in patients with age-related macular degeneration. METHODS: Visual acuity was measured in four sessions over 12 weeks using a standardized protocol with ETDRS charts in 107 nontreated eyes of 107 patients with age-related macular degeneration enrolled in an ongoing clinical trial. RESULTS: Data from 90 patients were included in the analysis. The 95% coefficient of repeatability (CR) was 12 ETDRS letters and ranged from 9 letters for 29 eyes with small to intermediate drusen only to 17 letters for 25 eyes with late AMD (macular scars or geographic atrophy). Ten (11%) eyes had a 5-letter reduction or more in visual acuity at the week 1 visit compared with baseline. Excluding seven eyes with visual acuity measurements potentially affected by measurement-related factors (a change in testing distance between visits) the revised CR was 10 letters for the cohort (n = 83) and 11 letters for the late-AMD subgroup (n = 18). CONCLUSIONS: Intersession ETDRS visual acuity measurements are subject to considerable variability in patients with AMD. The variability may be due to both measurement- and disease-related factors. The variable readings have implications for AMD clinical trial design and for the assessment and treatment of patients with neovascular AMD. Further work is needed to determine both the sources of variability in visual acuity measurements and the optimal change criterion for visual acuity measurements in this important group of patients.

Schmitz-Valckenberg S, Fleckenstein M, Göbel AP, Sehmi K, Fitzke FW, Holz FG, Tufail A. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Am J Ophthalmol. · Pubmed #18514607 No free full text.

Abstract: PURPOSE: To compare fundus autofluorescence images (FAF) between a modified fundus camera (mFC) and a confocal scanning laser ophthalmoscope (cSLO). DESIGN: Evaluation of diagnostic technology. METHODS: Thirty-two eyes of 16 patients with age-related geographic atrophy (GA) treated in an institutional setting were included. FAF images were obtained with both the cSLO (excitation, 488 nm; emission, > 500 nm) and the mFC (excitation, approximately 500 to 610 nm; emission, approximately 675 to 715 nm). Using established algorithms, images were graded by two independent observers and agreements were evaluated. The main outcome measures were image quality, quantification of total atrophy, and classification of FAF patterns. RESULTS: In two eyes with advanced cataract (lens grade 7 according to the Age-Related Eye Disease Study classification), FAF image quality with both systems was not sufficient for any meaningful analysis. In the remaining 30 eyes, the mean differences of the interobserver agreements for atrophy quantification were 0.16 mm2 (95% confidence interval [CI], 0.07 to 0.38) for mFC and 0.15 mm2 (95% CI, -0.04 to 0.33) for cSLO images. Because of inferior signal-to-noise ratios, FAF pattern classification was possible in a lower number of mFC images (69%) compared with cSLO images (88%). CONCLUSIONS: This study suggests that the agreements for atrophy quantification are similar with both devices. The lesser visualization of FAF patterns with the mFC and thus inferior determination of disease markers may be the result of the nonconfocality and the use of single instead of mean images compared with the cSLO. These findings may be important for the design of interventional trials as well as the routine use of FAF imaging in age-related geographic atrophy.

Patel PJ, Chen FK, Ikeji F, Xing W, Bunce C, Da Cruz L, Tufail A. · Moorfields Eye Hospital, London, United Kingdom. · Invest Ophthalmol Vis Sci. · Pubmed #18326734 links to  free full text

Abstract: PURPOSE: To determine the repeatability of Stratus optical coherence tomography (OCT) measures of retinal thickness and volume in patients with neovascular age-related macular degeneration (nAMD) METHOD: Fifty-one eyes of 51 consecutive patients with nAMD underwent an OCT imaging session in which two fast macular thickness map (FMTM) protocol scans sets were acquired by a single experienced operator certified for clinical trials work. Coefficients of repeatability for each of nine Early Treatment of Diabetic Retinopathy Study (ETDRS)-like regions, foveolar center-point retinal thickness (CPT) and total macular volume (TMV), were calculated. Scans were analyzed retrospectively for errors in retinal boundary placement by two observers, with revised coefficients of repeatability calculated after excluding any scan sets with significant segmentation error. RESULTS: The coefficient of repeatability for the central 1-mm macular subfield was 67 mum (23%) and was less than 75 mum for all macular subfields. There was much larger variability in the center-point thickness measure, with a coefficient of repeatability of 88 mum (32%) for the automated center-point thickness (ACPT). After excluding nine scan set pairs with significant segmentation error, the coefficient of repeatability for the central 1-mm macular subfield was reduced to 50 mum (19%). CONCLUSIONS: OCT-derived retinal thickness measurements are subject to considerable measurement variability in patients with nAMD. Changes in central macular thickness of more than 50 mum may better reflect true clinical change in scan sets without significant segmentation error and may be used to guide the retreatment of patients with nAMD in clinical trials and clinical practice.

Uppal G, Milliken A, Lee J, Acheson J, Hykin P, Tufail A, da Cruz L. · Moorfields Eye Hospital, London, UK. · Clin Experiment Ophthalmol. · Pubmed #17651250 No free full text.

Abstract: PURPOSE: We propose a case selection algorithm to assess suitability for macular translocation for subfoveal neovascular membrane (CNV) secondary to age-related macular degeneration. The algorithm is based on preoperative assessment of residual foveal function, as assessed by a slit-lamp fixation task and duration of visual loss, in patients with poor acuity. We validate our slit-lamp fixation task against an objective analysis (Nidek MP-1 Microperimetry) and proceed to examine surgical outcomes as selected by the algorithm. METHODS: A prospective series of 27 consecutive patients with CNV underwent translocation at Moorfields Eye Hospital, London between May 2003 and May 2006. RESULTS: Validation of the slit-lamp fixation task revealed 100% concordance in classification of fixation between the slit-lamp task and the microperimeter. At an average follow up of 12.2 months, the mean Early Treatment of Diabetic Retinopathy Study distance acuity improved from logMAR 0.88 to 0.68 (P < 0.03). Sixty-six per cent of patients achieved an acuity of < or =logMAR 0.8 (6/30), 22% an acuity of < or =logMAR 0.3 (6/12) and 33% gained three lines of acuity. The mean MN Read reading acuity improved from logMAR 1.23 to 0.91 (P < 0.01). Forty-four per cent of patients achieved an acuity of > or =logMAR 0.7 (N10), 15% an acuity of > or =logMAR 0.4 (N5) and 44% gained three lines of acuity. DISCUSSION: We have demonstrated a simple case selection algorithm that is based on residual foveal function and suggests good outcomes. The strongest indicators of foveal function are fixation characteristics and duration of visual loss. In contrast to previous studies, our algorithm suggests good outcomes independently of preoperative visual acuity and CNV characteristics.

Essex RW, Tufail A, Bunce C, Aylward GW. · Moorfields Eye Hospital, City Road, London EC1V 2PD, UK. · Br J Ophthalmol. · Pubmed #17446505 No free full text.

Abstract: PURPOSE: To present the 2-year outcomes of surgical removal of non-age-related macular degeneration (AMD)-related choroidal neovascular membranes and to evaluate any association between visual outcome and baseline clinical factors. METHODS: Retrospective consecutive case series. All patients who had surgery for non-AMD-related choroidal neovascularisation (CNV) between November 1997 and March 2003 under the care of a single surgeon (WA) were included in the study. Baseline data including patient age, duration of subfoveal CNV, preoperative visual acuity (VA), lesion size, lesion components and aetiology were collected. The primary outcome was VA change with secondary outcomes retinal detachment, operative peripheral retinal break formation, CNV recurrence and cataract. RESULTS: A total of 52 eyes were included in the study. The aetiology of CNV was: punctate inner choridopathy 21 (40%); idiopathic 8 (15%); pathologic myopia 6 (12%); ocular histoplasmosis syndrome 1 (2%); and other 16 (31%). The mean age of patients was 41(range 14-72) years. 24-month follow-up was available for 41 (80%) eyes. The mean logMAR equivalent baseline acuity was 1.1 and mean lesion size 1.2 disc areas. An improvement in VA >1 Snellen line was noted in 26 (63%) eyes, whereas 10 (24%) eyes remained the same (within 1 line) and 5 (12%) lost >1 line of acuity. Improvement in VA was associated with worse baseline VA (84% for eyes with VA <or=6/36 vs 31% for those with VA>6/36, p=0.001). No evidence of association between 2-year visual outcome and any other baseline factor under study was observed. Peripheral retinal breaks were noted in 5 (10%) eyes at the time of surgery, and 3 (5.8%) eyes developed postoperative retinal detachments. Persistent/recurrent CNV was noted in 17 (33%) eyes. The median time to presentation of CNV in these eyes was 27 (range 2-172) weeks. Five eyes underwent cataract surgery during the follow-up period. The mean age of these patients was significantly higher than the mean age of those who did not require cataract surgery (57 vs 37 years, p=0.014). CONCLUSIONS: Surgical excision of non-AMD-related CNV resulted in improvement of VA in the majority of eyes. Worse presenting acuity was associated with better visual improvements.

MacLaren RE, Uppal GS, Balaggan KS, Tufail A, Munro PM, Milliken AB, Ali RR, Rubin GS, Aylward GW, da Cruz L. · Moorfields Eye Hospital, City Road, London, UK. · Ophthalmology. · Pubmed #17324698 No free full text.

Abstract: PURPOSE: To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). DESIGN: Prospective interventional cohort study. PARTICIPANTS: Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy. METHODS: Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch's membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. MAIN OUTCOME MEASURES: Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. RESULTS: Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically modified outside the eye with a viral vector applied within the time frame of the operation. CONCLUSIONS: Autologous RPE transplantation can in principle restore vision in neovascular AMD, but surgical complications remain high. The possibility for ex vivo gene transfer to the free graft of RPE may widen the scope of this procedure to include gene therapy or adjunctive molecular treatments for AMD.

Neveu MM, Tufail A, Dowler JG, Holder GE. · Moorfields Eye Hospital, London, EC1V 2PD, UK. · Doc Ophthalmol. · Pubmed #16972084 No free full text.

Abstract: This study compares pattern electroretinography (PERG) and multifocal electroretinography (mfERG) measures in 13 patients with predominantly classic choroidal neovascularisation (CNV) associated with age-related macular degeneration (ARMD, 9/13 unilateral, 4/13 bilateral), assesses the usefulness of each test in monitoring disease progression, and identifies electrophysiological predictors of outcome following treatment with photodynamic therapy (PDT). PERG and mfERGs were recorded at presentation, 2 weeks post-treatment, and at 3 monthly intervals for 2 years. The PERG was detectable in 8/13 patients with unilateral disease; the mfERG was detectable in 12/13 patients. P50 and N95 amplitudes increased in 6/8 patients and mfERG p1 increased in 7/13 patients at 2 years. PERG amplitudes correlated strongly with mfERG amplitudes in patients with unilateral disease. PERG P50 and mfERG p1 amplitude correlated with visual acuity at 2 years (R = 0.68, R = 0.82, respectively). The largest PERG P50 and mfERG p1 amplitude difference between treated and fellow eyes of all the groups on initial visit was associated with a poor visual outcome (P50 64% difference; p1 29% difference) whereas those with the smallest P50 and p1 amplitude difference was associated with improved vision at 2 years (P50 30% difference; p1 21% difference). The PERG and mfERG provide an objective measure of central retinal function in the progression of ARMD. A detectable PERG on presentation was the single best indicator of improved function and visual acuity at 2 years. The mfERG demonstrated disease progression from central retina into the paramacular regions over 2 years. Patients with poor visual outcomes had the largest inter-ocular amplitude difference on presentation, suggesting that such patients may have a worse prognosis following treatment.

Lengyel I, Tufail A, Hosaini HA, Luthert P, Bird AC, Jeffery G. · Experimental Age Related Macular Degeneration Research Group, Institute of Ophthalmology, University College London, London, United Kingdom. · Invest Ophthalmol Vis Sci. · Pubmed #15326099 links to  free full text

Abstract: PURPOSE: To determine the pattern of drusen accumulation with age and to investigate the initial sites of deposition and their relationship to choroidal capillaries in human donor eyes from the eye bank of Moorfields Eye Hospital. METHODS: Wholemounted, hydrated preparations of the choriocapillaris and Bruch's membrane from donor eyes ranging from 42 to 95 years, with or without retinal pigment epithelium (RPE), were examined by conventional and confocal microscopy. Drusen were visualized by their autofluorescence. RESULTS: In all age groups studied autofluorescent drusen were present at the equator but were not found centrally where the vascular architecture is different, being tubular rather than a honeycomb pattern. Autofluorescing drusen were strongly associated with the lateral walls of the choriocapillaris (an area commonly known as the intercapillary pillars of the choriocapillaris (P = 0.028; Wilcoxon signed ranks test). Nonfluorescing drusen were occasionally seen centrally, but were not easily identified, and because of their large size, their localization with respect to capillary walls was not possible. CONCLUSIONS: These results strongly support the notion that autofluorescent drusen are not randomly distributed and have a specific spatial relationship to choroidal vessel walls. That equatorial drusen fluoresce, whereas central drusen do not, suggests that they may have different chemical compositions at the two sites and possibly different significance in age-related macular disease.